Biomedical subjects
Publications and source records attributed to K Ishihara.
The regional distribution of mucus glycoprotein in lamb before weaning and sheep was studied. Mucus glycoprotein was present in the forestomach region of lamb and glandular stomach (abomasum) of lamb and sheep. Ester sulfates were found in all mucus glycoproteins obtained.
Tris(hydroxymethyl)aminomethane (Tris) has been shown to inhibit selectively the Golgi apparatus and Golgi-endoplasmic reticulum-lysosomal system (GERL system) of several kinds of cells including pancreatic B cells. This study was designed to assess the effect of Tris on insulin, glucagon and somatostatin release and insulin synthesis in pancreatic B cells by using isolated rat pancreatic islets. Tris suppressed glucose-induced insulin release, whereas it did not affect the glucagon and somatostatin release. Furthermore, the incorporation of [3H]leucine into the insulin fraction was suppressed by 10 mM Tris, but the sum of the radioactivity of both proinsulin and insulin fraction were not influenced. The present study suggests that the Golgi apparatus and GERL system may play a role in insulin secretion and biosynthesis in pancreatic B cells.
The in vitro growth of Streptococcus mutans was completely inhibited by water-soluble extracts from cells of various intestinal lactic acid bacteria identified as Streptococcus faecium, Streptococcus equinus, Lactobacillus fermentum, and Lactobacillus salivarius. The growth inhibition was dependent on the concentrations of the extracts. In contrast, the extracts did not inhibit the growth of the major indigenous intestinal lactic acid bacteria isolated from humans. These lactic acid bacteria were not acutely toxic in mice.
Radiolabeled glycoconjugates were prepared by incorporation of [35S]sulfate and [3H]glucosamine into the gastric mucosa of human gastric resection specimens, using organ culture techniques. Specimens which incorporated higher amounts of [35S]sulfate into high molecular glycoconjugates (Fr-1) were designated as group I. The average specific activity in Fr-1 of group I was 30 times that of group II, but the glucosamine uptake remained about the same in all cases. All specimens in group I were positive to intestinal metaplasia in their adjacent mucosal area. The sulfated glycoproteins in Fr-1 of group I were found to incorporate 80% of the 35S and the remaining 20% by sulfated glycosaminoglycans. But the glycoconjugates constituting all the Fr-1 of group II were identified as glycoproteins and incorporating 35S only to a small extent were identified as sulfated glycoproteins. The susceptibility of the glycoproteins from group I mucosa to pronase digestion was different from that of group II. The glycoproteins synthesized in group I mucosa were as sulfated glycoproteins as well as nonsulfated glycoproteins and glycosaminoglycans, while the group II glycoproteins consisted primarily of nonsulfated glycoproteins.
The aortic regurgitant fraction was estimated noninvasively in 20 patients with aortic regurgitation from systolic aortic and pulmonary volume flow determined by duplex Doppler echocardiography. By assuming that an excess of the aortic volume flow (AF) compared with the pulmonary volume flow (PF) is due to aortic regurgitant flow, the aortic regurgitant fraction (RF) was calculated as follows: RF(%) = (AF - PF)/AF X 100. The aortic and pulmonary volume flows were determined as products of systolic integrals of ejection flow velocities and cross-sectional areas of the left and right ventricular outflow tracts, respectively. The Doppler estimate of the regurgitant fraction was compared by semiquantitative grading (1+ to 4+) by cineaortography and with the measurement of regurgitant fraction by catheter technique. The mean Doppler-determined aortic regurgitant fraction was 2.4% for normal subjects, 28.0% for the patients with 1+, 32.6% for the patients with 2+, 53.3% for the patients with 3+, and 62.4% for the patients with 4+. A fair correlation was found between Doppler estimates of regurgitant fraction and semiquantitative cineaortographic grades (r = .80, p less than .01). In the patients without associated mitral regurgitation, a close correlation was observed between Doppler and catheter estimates of regurgitant fraction (r = .96, p less than .01; y = 1.0x - 0.08). In the patients with associated mild mitral regurgitation, however, Doppler estimates of regurgitant fraction substantially underestimated those determined by the conventional catheter technique, which cannot separately quantitate the aortic regurgitant fraction in the presence of mitral regurgitation. These observations indicate that the proposed Doppler technique provides a useful method to evaluate the aortic regurgitant fraction specifically regardless of the presence of associated mitral lesions.
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Malignant melanoma is one of the most malignant froms of cancer, for which the prognosis is still very grave. However, it need not necessarily be regarded as such a fearful tumor if it is found at an early stage and treated thoroughly and adequately. An understanding of the early clinical changes in the size, color and shape of the tumor is required, and early discovery can save a patient's life. Histopathological examination should be done for diagnosis, and S-100 protein should be checked together with monoclonal antibody studies sometimes. The main principle of treatment in the early stage of malignant melanoma is to make an incision 2 to 5 cm away from the edge of the tumor. As a rule, exploratory excision and minor resection should not be performed. It may be said, accordingly, that multidisciplinary treatment should only be given for malignant melanoma of stage 1b and more advanced stages. At present, chemotherapeutic combinations used as the first choice in Japan are two regimens, one of which is DAV (DTIC, ACNU and vincristine), and the other, PAV (peplomycin, ACNU and vincristine). The effectiveness rate with DAV and PAV have been approximately 30% in various clinical studies. Favorable clinical responses obtained by radiotherapy have often been observed after fast neutron irradiation and hyperthermia therapy. Immunotherapy and interferon treatment are also often applied for malignant melanoma.
We have performed a co-operative controlled clinical study of Bestatin in the treatment of malignant tumors of the skin at 18 research institutions in Japan. Twenty-seven Bestatin-treated cases of stage I and II squamous cell carcinoma and 24 control cases were followed up for a maximum of 46 months, to compare disease-free and survival rates in the 2 groups. There was no significant difference in either rate between the groups, though each rate was slightly higher for the Bestatin-treated group. Eight Bestatin-treated cases of genital Paget's disease and 8 control cases were similarly followed up. The survival rate was slightly higher for the Bestatin-treated group, but each group consisted of too small a number of cases to demonstrate the utility of Bestatin. The data obtained up to now only suggest the future potentiality of Bestatin treatment for these types of malignancy. For this reason, the data from phase III studies of Bestatin, including previously reported findings on malignant melanoma, proved Bestatin to be useful in treating stage Ib and II malignant melanoma, but were only suggestive of its potential indication in the treatment of other malignant tumors of the skin. Although Bestatin was administered for long periods (a mean of 21.5 months), only mild gastrointestinal disturbances were observed as adverse reactions to the drug in 4.5% of cases.
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Kaposi's sarcoma (KS) is a very rare disease in Japan. The description by Moritz kaposi in 1872 of a "multiple idiopathic pigment sarcoma of the skin" stressed the multifocal lesions of the disease and its vascular nature, and it was renamed multiple idiopathic hemorrhagic sarcoma." For many years, the traditional form of KS was seen by most dermatologists and pathologists. During the 1970s, following the initiation of immunosuppression therapy for kidney transplantation, on autoimmune disease, KS was observed to occur in up to 5% of patients undergoing this procedure. In 1981, reports began to appear of kaposi's sarcoma in young immunocompromised homosexual men. Many patients bad lymphadenopathy and/or unusual opportunistic infections. The clinical manifestations of traditional KS were and are well established. The initial lesions usually involve the lower extremities, beginning as macules and patches and extending to plaques and modules. The color is thought to be somewhat distinctive, especially in the later stages, with hues of red or red-brown with a bluish purple tone. Eventually, non-pitting edema of the legs is seen, with widely scattered involvement of cutaneous lymph nodes and eventually, internal organs. The disease is considered to be multifocal both in the traditional and AIDS-associated (new KS) forms. The clinical course of the disease is variable. The differential diagnosis of KS has become a major problem in histopathology. Factor-VIII-related antigen may be demonstrated in vascular endothelium using immunoperoxidase staining methods and may be useful, as a practical approach to skin biopsy in high-risk patients, awareness of the differential diagnoses is of primary importance. An abnormal helper: suppressor ratio of T lymphocytes is found in most of the immunocompromised groups, KS patients are treated by radiation and/or chemotherapy. Some drugs are well-suited for the long-term treatment of KS.
Febrile episodes in 147 patients undergoing first remission induction therapy for acute leukemia were analyzed. Febrile episodes occurred 254 times in 136 patients. The cause of fever could not be identified in 54.3% of all episodes. Antibiotic therapy was effective in 81.1% of these episodes with no cause determined. Postmortem examinations proved infections in 65.2% of patients who had fever of unknown origin before death. Sepsis and pneumonia together accounted for 53.4% of documented infections. Sepsis and pneumonia occurred most often when the patients had neutropenia (less than 500/mm3). Increase in neutrophil count and achievement of hematologic remission produced good prognosis of the infections, and the reverse was also true in some patients. Fifty percent of fetal patients died of infection. The incidence of infections, especially pneumonia and infections caused by fungi and Proteus species indicating such infections were exogenous, reduced markedly in laminar air flow rooms.
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As a co-operative study involving 18 medical research institutions, we have made a randomized, controlled study (phase III study) of Bestatin in the treatment of malignant melanoma (stage Ib, II) over the last 4 years. The results were as follows; Bestatin significantly prolonged disease-free intervals by 9-20 month. Bestatin significantly prolonged survival periods by 10-16 months. Side effects of Bestatin, chiefly comprising of reversible gastro-intestinal disturbances, were observed in 7.1% of Bestatin-treated cases. These findings suggest that Bestatin is a very useful agent for treating for stage Ib and II malignant melanomas.